1 Invasive and non-invasive quantification of myocardial fibrosis in primary mitral regurgitation: prognostic implications for post-operative remodelling, symptom burden and exercise capacity

Chronic primary mitral regurgitation (MR) exposes the left ventricle (LV) to volume overload and is associated with evidence of fibrosis on non-invasive imaging. It is not known whether fibrosis predicts outcome from surgery. This study aimed to 1) quantify myocardial fibrosis on histology and non-invasive imaging, 2) investigate any association between fibrosis and LV size and function, 3) determine the impact of fibrosis on post-operative outcome. Methods In a prospective observational multicentre study, 105 patients with severe MR (N=65/32/8 NYHA Class I/II/III respectively; mean age 63.1±13.4years; male 73%; VO2max 91.2±22.4%) had multiparametric cardiac magnetic resonance (CMR), symptom assessment (Minnesota Living with Heart Failure Questionnaire (MLHFQ)) and cardiopulmonary exercise testing before and at 6-9 months following repair. Patients consented for up to 3 intraoperative LV biopsies for histological collagen volume fraction (CVF) quantification. Results 234 LV biopsies were collected from 86 patients with median CVF of 14.6%[IQR 7.4-20.3]. Fibrosis was present even in NYHA Class I patients (13.6%[6.3-18.8]), and was significantly higher than the 3.3%[2.6-6.1] obtained from 8 autopsy controls without cardiac disease (P Pre-operatively, there was no relationship between CVF and LV size, systolic function, ECV, late gadolinium enhancement, although CVF did correlate with MLHFQ (R=0.23, P=0.034). Conversely, ECV correlated with systolic (LVEF Rho=-0.22, P=0.029; LVESVi Rho 0.22, P=0.025, GCS Rho=0.31, P=0.002) and diastolic function (E/e’ R=0.25, P=0.022), exercise capacity (%VO2max R=-0.22, P=0.030), with borderline correlation to MLHFQ (R=0.19, P=0.058). Following surgery, although LVEF remained >50% in all but 6 patients (LVEF pre 69.1±8.0 vs post 63.3±8.3%, P Conclusions Myocardial fibrosis is present in primary MR, before the onset of symptoms. Due to its patchy nature, ECV but not fibrosis on histology is a better marker of pre-operative myocardial function and symptom status. Despite ECV reduction following successful MR surgery, symptomatic patients fail to regain exercise fitness and symptom-free status – providing further support for the benefits of early surgery. Conflict of Interest None